Brain implantable electrodes having an increased signal to noise ratio and method for making same

ABSTRACT

Herein disclosed are an electrode and a method for making an electrode having an enhanced electrically effective surface providing an increased signal to noise ratio. The electrode having a metal surface selected from gold, tungsten, stainless steel, platinum, platinum-tungsten, platinum-iridium, and combinations thereof; and an electrically conductive coating on said metal surface, said coating consisting essentially of polymerized pyrrole.

RELATED APPLICATION

This application claims priority from co-pending provisional applicationSer. No. 60/758,420, which was filed on Jan. 12, 2006, and which isincorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to the field of microelectrodes and, moreparticularly, to microelectrodes especially configured for obtainingelectrical signals from the brain.

BACKGROUND OF THE INVENTION

Researchers have, for many years, employed electrodes implanted directlyinto the brains of experimental animals for obtaining electrical datafrom brain tissue. Challenges in this endeavor have been the types ofmetals that are amenable for such use without causing adverse biologicalreactions and the size of theses electrodes, as well as limitations intheir available surface area for collecting the weak electrical signalsproduced in the brain. Therefore, increasing the signal to noise ratiofor brain-implantable electrodes has been one parameter needingimprovement.

SUMMARY OF THE INVENTION

With the foregoing in mind, the present invention advantageouslyprovides brain-implantable electrodes coated with a layer of anelectrically conductive polymer and a method for making such electrodes.

In a preferred embodiment of the present invention, an electrode havingan enhanced electrically effective surface providing an increased signalto noise ratio comprises a metal surface selected from gold, tungsten,stainless steel, platinum, platinum-tungsten, platinum-iridium, andcombinations thereof, and an electrically conductive coating on saidmetal surface, said coating consisting essentially of polymerizedpyrrole. In this electrode, the polymerized pyrrole coating provides aplurality of surface microcavities. That is, the electrically conductivecoating forms a new surface on said electrode, said new surface disposedwith a plurality of microcavities which increase total electricallyeffective surface on said electrode, thereby causing said electrode tohave an increased signal to noise ratio. The electrically conductivecoating has a surface disposed with a plurality of microcavities of upto 500 nm in depth and separation.

The present invention also includes a method of increasing theelectrically effective surface area of an electrode. The methodcomprises connecting a metal electrode to a positive terminal in anelectrolytic chamber having negative terminal and a power supply capableof delivering a constant amperage. The method continues by adding to thechamber a volume of an electrolytic bath so that the electrode issubmerged therein, the electrolytic bath consisting essentially ofdistilled water, a soluble concentration of pyrrole, 98%, a solubleconcentration of p-toluene-sulfonate, 95%, and mercapto-ethane-sulfonicacid in approximately one tenth the concentration of pyrrole andp-toluene-sulfonate. Finally, the method calls for coating the electrodewith an electrically conductive layer of polymerized pyrrole byenergizing the power supply to pass through the electrolytic bath acurrent of approximately 1 μAmp for a time sufficient to effectdeposition of polymerized pyrrole on the electrode. In the method, it ispreferred that the metal electrode contain one or more metals selectedfrom gold, tungsten, stainless steel, platinum, platinum-tungsten,platinum-iridium, and combinations thereof. In practicing the method,deposition may be monitored and/or verified by measuring to determinethat the depositing step causes a decrease in electrode impedance. Thedecrease in electrode impedance should be proportional to the amount ofcoating deposited. Additionally, depositing provides the electrode witha plurality of microcavities formed in the deposited electricallyconductive layer.

In the method of coating, the chamber contains an electrolytic solutionconsisting essentially of a volume of distilled water, a solubleconcentration of pyrrole, 98%, a soluble concentration ofp-toluene-sulfonate, 95%, and mercapto-ethane-sulfonic acid inapproximately one tenth the concentration of pyrrole andp-toluene-sulfonate. More specifically, in the electrolytic solution thevolume of distilled water is approximately 50 ml, the soluble molarconcentration of 98% pyrrole is approximately 0.1 M, the soluble molarconcentration of 95% p-toluene-sulfonate is approximately 0.1 M, and themercapto-ethane-sulfonic acid molar concentration is approximately 0.01M.

BRIEF DESCRIPTION OF THE DRAWINGS

Some of the features, advantages, and benefits of the present inventionhaving been stated, others will become apparent as the descriptionproceeds when taken in conjunction with the accompanying drawings,presented for solely for exemplary purposes and not with intent to limitthe invention thereto, and in which:

FIG. 1 displays macroelectrodes showing conductive polymer coatings ofpolypyrrole and polyaniline: on the left, polypyrrole; center,polyaniline with a higher deposition current; right, polyaniline with alower deposition current; all according to an embodiment of the presentinvention;

FIG. 2 depicts single-unit recordings and isolated neural actionpotentials and shows an actual recording of data taken using ourconductive polymer coating with microelectrodes in an anesthetizedhamster;

FIG. 3 is a flow diagram of the process and technical parameters inobtaining viable multiple electrode array (MEA) experimental results(Source: Multi-Channel Systems website, a partner to Product Licensee#2,ALA Scientific Instruments);

FIG. 4 shows an MEA for “in-vitro” type brain slice experiments;

FIG. 5 illustrates an MEA with live tissue and an overlay of neuralsignals from the tissue;

FIG. 6 is a photograph of the exposed metal tips of an insertionmicroelectrode array; three of eight tips are shown; spacing betweenelectrodes is approximately 400 micrometers; length of this array isapproximately 30 millimeters;

FIG. 7 is a scanning electron microscope (SEM) photograph of the tip ofan insertion microelectrode, shank diameter of approximately 40 microns;and

FIG. 8 is an atomic force microscope (AFM) photograph of the depositionof our conductive polymer coating on a flat macro-electrode.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The present invention will now be described more fully hereinafter withreference to the accompanying drawings, in which preferred embodimentsof the invention are shown. Unless otherwise defined, all technical andscientific terms used herein have the same meaning as commonlyunderstood by one of ordinary skill in the art to which this inventionpertains. Although methods and materials similar or equivalent to thosedescribed herein can be used in the practice or testing of the presentinvention, suitable methods and materials are described below. Anypublications, patent applications, patents, or other referencesmentioned herein are incorporated by reference in their entirety. Incase of conflict, the present specification, including any definitions,will control. In addition, the materials, methods and examples given areillustrative in nature only and not intended to be limiting.Accordingly, this invention may, however, be embodied in many differentforms and should not be construed as limited to the illustratedembodiments set forth herein. Rather, these illustrated embodiments areprovided so that this disclosure will be thorough and complete, and willfully convey the scope of the invention to those skilled in the art.Other features and advantages of the invention will be apparent from thefollowing detailed description, and from the claims.

FIGS. 1-8 illustrate various aspects of the present invention. In thatregard, FIG. 1 depicts the first success of coating our macro-electrodeswith a special conductive polymer was obtained after we tested variousconductive polymer coatings under different protocols usingmacro-electrodes as shown. The macro-testing procedure was helpful inquickly testing the adhesion, consistency and porous layering of thepolymer coating.

We utilized the SEM and Atomic Force Microscope to physically observeand measure the three dimensional nature of the coating. We alsodetermined the basic electrolytic bath and electronic setup to controlthe deposition process. We set up the ongoing deposition process andanimal testing and found a specific deposition protocol to give us theporosity we required. We found that we could deposit our conductivepolymers on different metals, such as: gold, tungsten, stainless steel,platinum, platinum-tungsten and platinum-iridium. These are the metalsthat have been found through experience that the brain finds friendlyand without toxic reactions. For instance, typically, it is known thataluminum and silver are not suitable for use in brain implants remainingin the brain longer than approximately 2 days, due to toxic reactions.

For neural recordings, data acquisition was accomplished with theTucker-Davis system, which allowed us to graphically record all neuralsignals for our experiments. For example, the upper portion of FIG. 2shows actual data of one of our olfactory single-unit microelectroderecordings, which captures three separate neural signals (lower portionof FIG. 2) on a single recording channel. These microelectrodes werecoated with our conductive polymer. We can correlate these neuralactivities with a sensory cue of a specific odor and can determineexactly which neuron is odor sensitive and its pattern of activityrelated to the odor. FIG. 2 shows an actual recording of data takenusing our conductive polymer coating with microelectrodes in ananesthetized hamster. The data obtained exhibited an estimated 2:1increase in the signal-to-noise ratio as compared to signal strengthsobtained in over 20 previous experiments using uncoated electrodes.

The technical parameters shown in FIG. 3 were used when recording from aMultiple Electrode Array (MEA). These technical considerations are quitesimilar to those required to obtain good single and multiple unit datain an awake animal. In order to get proper recordings, as those shown inFIG. 2, the signal shaping is mainly controlled by the electrodegeometry, impedance and noise. Our conductive polymer coating allows theresearcher to achieve more control over the impedance and drive thenoise down, which results in a higher signal-to-noise ratio. Thisdelivers a significantly improved signal, thereby enabling theresearcher to complete the sensory analyses, as opposed to not beingable to distinguish the noise from the signal. These principles apply torecordings from any brain area and to over 200 types of insertionelectrodes. Such an improvement of signal-to-noise ratio as disclosed inthe present invention enables smaller signals to be revealed andrecorded, thereby allowing a better understanding of brain function inthe recorded area.

FIG. 4 shows an actual MEA device without any incubated brain slices.FIG. 5 shows an incubated brain slice and neural recordings from thatincubated tissue. FIG. 6 shows a sample (only one of hundreds) ofinsertion electrodes. Over 95% of researchers who obtain neuralrecordings from animals and humans do so by using some form of insertionmicroelectrodes. These insertion electrodes range in diameter from 40microns to 500 microns and in length from 2 millimeters to over 80millimeters. Some deep brain studies in human require electrodes over 8inches in length.

Process for Coating Microelectrodes with the Conductive Polymer.

A. The process begins with an electrolytic bath. We prepared thechemical solution for the electrolytic bath as follows:

-   -   1. Add 50 ml of distilled water to a clean electrolytic chamber.        The circular negative electrolytic plate was made of heavy gauge        platinum wire.    -   2. Add 0.1M of Pyrrole, 98%.    -   3. Heat 50 degrees C. and stir into solution for 5 minutes.    -   4. Add 0.1M of Sodium p-toluene-sulfonate, 95%.    -   5. Continue heating and stir for another 5 minutes.    -   6. Add 0.01M of MES (mercapto-ethane-sulfonic acid).    -   7. Continue heating and stir for another 5 minutes.

B. Once a fresh batch of the electrolytic solution is prepared, hook upthe insertion-type microelectrodes to the positive connection of theconstant amperage isolation unit. The plating protocol is as follows.

-   -   1. Insert the metal tips of the microelectrodes into the        electrolytic bath making certain that the microelectrodes are        positioned in the center area of the curved negative plate. This        will promote formation of an even coating of conductive polymer        on the microelectrode tips.    -   2. Record the impedance of each microelectrode before starting        the deposition process. These values will typically vary between        1 MegOhm and 10 MegOhms.    -   3. Pump in 1 microAmp of current through the microelectrodes for        5 minutes via the isolation unit.    -   4. Verify and record the impedance measurement of each        microelectrode after the deposition process is complete. One        should observe a marked decrease in impedances. Normally a 3        MegOhm impedance will drop to 500-800K Ohms after deposition.    -   5. Further verification is done by observing the black coating        on the micro tips of the electrodes.

C. During the original experiments to develop this process, we used theboth the Scanning Electron Microscope (SEM) and the Atomic ForceMicroscope (AFM) to measure the micro-porosity of the conductive polymercoating. FIG. 7 shows an SEM photo (800×) of the tip of one insertionmicroelectrode. The ultra white area at the point is the exposed metalsurface of less than 5 microns; that is the area coated with ourconductive polymer. The microelectrode shown FIG. 8 shows an AFM photoof that process. One can clearly see micro-cavities ranging from 0nano-meters to 500 nano-meters in depth and separation.

D. After the electrodes are coated with the conductive polymer, we storethem in a foam holder within an enclosed plastic case. After six weeksof storage and without exposure to any oxidation process, we haveverified that the coated microelectrodes still have the same lowimpedance as freshly coated microelectrodes.

In summary, the end-product delivers a high performance microelectrodeand has the following qualities.

1. The coating is long lasting and it does not wear off in brain tissue.

2. The coating strongly adheres to large (i.e. macro) and small surfaceareas (typically less than 500 sq. microns) on at least the followingmetals: gold, tungsten, stainless steel, platinum, platinum-tungsten andplatinum-iridium.

3. The coating has a porous structure, thereby resulting in lowerimpedance microelectrodes, presumably due to the greatly increasedsurface area provided within the z-dimension by the polymer coating.This results in a significant improvement in signal-to-noise ratio.

4. The method of coating makes it easy to coat insertion microelectrodesand MEAs.

5. This coating significantly outperforms any other coating known to theinventors.

Accordingly, in the drawings and specification, there has been discloseda typical preferred embodiment of the invention, and although specificterms are employed, the terms are used in a descriptive sense only andnot for purposes of limitation. The invention has been described inconsiderable detail with specific reference to these illustratedembodiments. It will be apparent, however, that various modificationsand changes can be made within the spirit and scope of the invention asdescribed in the foregoing specification and as defined in the appendedclaims.

1. A method of increasing the electrically effective surface area of anelectrode, the method comprising: connecting a metal electrode to apositive terminal in an electrolytic chamber having negative terminaland a power supply capable of delivering a constant amperage; adding tothe chamber a volume of an electrolytic bath so that the electrode issubmerged therein, the electrolytic bath consisting essentially ofdistilled water, a soluble concentration of pyrrole, 98%, a solubleconcentration of p-toluene-sulfonate, 95%, and mercapto-ethane-sulfonicacid in approximately one tenth the concentration of pyrrole andp-toluene-sulfonate; and coating the electrode with an electricallyconductive layer of polymerized pyrrole by energizing the power supplyto pass through the electrolytic bath a current of approximately 1 μAmpfor a time sufficient to effect deposition of polymerized pyrrole on theelectrode.
 2. The method of claim 1, wherein the metal electrodecontains one or more metals selected from gold, tungsten, stainlesssteel, platinum, platinum-tungsten, platinum-iridium, and combinationsthereof.
 3. The method of claim 1, wherein depositing causes a decreasein electrode impedance.
 4. The method of claim 1, wherein depositingprovides the electrode with a plurality of microcavities formed in thedeposited electrically conductive layer.
 5. The method of claim 1,wherein decrease in electrode impedance is proportional to depositing.6. An electrolytic solution consisting essentially of: a volume ofdistilled water; a soluble concentration of pyrrole, 98%; a solubleconcentration of p-toluene-sulfonate, 95%; and mercapto-ethane-sulfonicacid in approximately one tenth the concentration of pyrrole andp-toluene-sulfonate.
 7. The electrolytic solution of claim 6, whereinthe volume of distilled water is approximately 50 ml, the soluble molarconcentration of 98% pyrrole is approximately 0.1 M, the soluble molarconcentration of 95% p-toluene-sulfonate is approximately 0.1 M, and themercapto-ethane-sulfonic acid molar concentration is approximately 0.01M.